Ulcers and gastritis.
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Endoscopy, Gastrointestinal↗
Biomedical subjects
F K Chan
Publications and source records attributed to F K Chan.
Comparison of two new rapid serology tests for diagnosis of Helicobacter pylori infection in Chinese patients.
BACKGROUND: Rapid serology test is a simple and convenient way for diagnosing Helicobacter pylori infection. However performances of these tests are usually less satisfactory than expected, particularly in developing countries. AIM: To evaluate the performances of two newly developed rapid serology tests for Helicobacter pylori infection. PATIENTS: Consecutive Chinese dyspeptic patients undergoing upper gastrointestinal endoscopy. METHODS: Gastric biopsies were obtained from antrum and corpus for rapid urease test and histological examination. Diagnosis of Helicobacter pylori infection was based on two or more positive results in rapid urease test, histology and [13C] urea breath test. Patients' sera were tested against two rapid serology tests: ASSURE Hp Rapid Test (Genelabs Diagnostics, Singapore) and SureStep (Applied Biotech, San Diego, CA, USA). RESULTS: A total of 148 patients were evaluated and Helicobacter pylori infection was diagnosed in 78 (53%) patients by gold standard. The sensitivities of ASSURE Hp and SureStep were, respectively, 94% and 71% (p=0.0003). Specificities of the two test kits were both 90%. The overall accuracy of ASSURE Hp was significantly higher than SureStep (92% versus 80%, p=0.004). CONCLUSION: Both rapid serology tests appear to be specific in diagnosing Helicobacter pylori infection in the Chinese populations. However the ASSURE Hp test is more sensitive and accurate than the SureStep test.
Adult↗
Alterations of frizzled (FzE3) and secreted frizzled related protein (hsFRP) expression in gastric cancer.
Wnt signaling pathway is important for development and carcinogenesis. Alterations of this pathway, such as mutations in adenomatous polyposis coli (APC) gene and activation mutations of beta-catenin, would result in stabilization of beta-catenin and subsequent translocation to nucleus where genes are transcribed. Recently, a receptor of Wnt, FzE3 was found to be up-regulated in esophageal carcinoma while a non-receptor antagonist of Wnt, secreted frizzled related protein (hsFRP) was found to be down-regulated in some cancer. These findings suggested that FzE3 is a potential oncogene while hsFRP is a potential tumor suppressor gene. We aimed to investigate whether FzE3 and hsFRP were altered in gastric cancer. Twelve cases of gastric cancer, including 7 cases of intestinal type, 4 cases of diffuse type and I case of mixed type, were studied. FzE3 and hsFRP mRNAs were expressed in most of the paired normal gastric tissues. FzE3 was over-expressed in 9 cases (75%) of gastric carcinoma tissues while hsFRP was down-regulated in 2 cases (16%). Beta-catenin nuclear staining was identified in 3 cases (27%) and cyclin D1 was expressed in 5 cases (41%) of cancer samples. All these cases were associated with either up-regulation of FzE3 or down-regulation of hsFRP. Our results suggested that alterations of FzE3 or hsFRP were frequent in gastric cancer. These provide alternative mechanisms leading to activation of Wnt signaling pathway in gastric carcinogenesis.
Adenocarcinoma↗
Fluorescence resonance energy transfer analysis of cell surface receptor interactions and signaling using spectral variants of the green fluorescent protein.
BACKGROUND: Fluorescence resonance energy transfer (FRET) is a powerful technique for measuring molecular interactions at Angstrom distances. We present a new method for FRET that utilizes the unique spectral properties of variants of the green fluorescent protein (GFP) for large-scale analysis by flow cytometry. METHODS: The proteins of interest are fused in frame separately to the cyan fluorescent protein (CFP) or the yellow fluorescent protein (YFP). FRET between these differentially tagged fusion proteins is analyzed using a dual-laser FACSVantage cytometer. RESULTS: We show that homotypic interactions between individual receptor chains of tumor necrosis factor receptor (TNFR) family members can be detected as FRET from CFP-tagged receptor chains to YFP-tagged receptor chains. Noncovalent molecular complexation can be detected as FRET between fusions of CFP and YFP to either the intracellular or extracellular regions of the receptor chains. The specificity of the assay is demonstrated by the absence of FRET between heterologous receptor pairs that do not biochemically associate with each other. Interaction between a TNFR-like receptor (Fas/CD95/Apo-1) and a downstream cytoplasmic signaling component (FADD) can also be demonstrated by flow cytometric FRET analysis. CONCLUSIONS: The utility of spectral variants of GFP in flow cytometric FRET analysis of membrane receptors is demonstrated. This method of analyzing FRET allows probing of noncovalent molecular interactions that involve both the intracellular and extracellular regions of membrane proteins as well as proteins within the cells. Unlike biochemical methods, FRET allows the quantitative determination of noncovalent molecular associations at Angstrom level in living cells. Moreover, flow cytometry allows quantitative analyses to be carried out on a cell-by-cell basis on large number of cells. Published 2001 Wiley-Liss, Inc.
Adaptor Proteins, Signal Transducing↗
Inverse association between cyclooxygenase-2 overexpression and microsatellite instability in gastric cancer.
This study examined the association between cyclooxygenase-2 (COX-2) overexpression and microsatellite instability (MSI) in gastric cancer. COX-2 expression was assessed by immunohistochemistry and scored in a semi-quantitative manner whereas MSI status was characterized by nine microsatellite markers. The clinicopathological features of cancers including survival data were analyzed. Of the 109 gastric cancers studied, COX-2 overexpression and high level of MSI (MSI-H) was detected in 64.2 and 22.0% cases respectively. Gastric tumors with MSI-H phenotypes had significantly lower level of COX-2 expression levels when compared to MSI-L and MSS tumors (P=0.002). Moreover, COX-2 overexpression was associated with tumor invasion beyond submucosa (P=0.045) and there was a trend favoring better survival in gastric cancers without COX-2 overexpression (P=0.07). The results from this study suggest that gastric cancer with microsatellite instability or COX-2 overexpression present with diverse clinicopathological features.
Cohort Studies↗
Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen.
BACKGROUND: Many patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients. METHODS: We studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months. RESULTS: We enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005). CONCLUSIONS: Among patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.
Anti-Bacterial Agents↗
Somatic beta-catenin mutation in gastric carcinoma--an infrequent event that is not specific for microsatellite instability.
We screened 90 cases of gastric carcinoma (GCA) samples for beta-catenin exon 3 mutation and assessed its possible relationship with microsatellite instability (MSI). Three mutations were detected in two samples, including a single mutation in an intestinal type and double mutations in a diffuse type GCA. One of the mutations found in the diffuse type GCA sample was a non-sense mutation at codon 68 (CAG-->TAG). This novel mutation was predicted to disrupt the binding of beta-catenin to alpha-catenin and may be related to the diffuse type morphology. The other two mutations were missense mutations involved or related to the GSK-3beta phosphorylation site, which have been reported previously. No MSI can be demonstrated in the two cases with beta-catenin mutation. Our results suggested that beta-catenin mutation was infrequent in GCA and appeared not specific for MSI.
Adult↗
Association between cyclo-oxygenase-2 overexpression and missense p53 mutations in gastric cancer.
Wild-type p53 competitively binds to the promoter region of COX-2 in vitro and inhibits its transcription. We examined the association between p53 mutation and COX-2 expression in gastric cancer. COX-2 over-expression was seen in 19 (48.7%) cases. These tumours had more lymph-node metastasis (P = 0.048) and tended to have a poorer survival (P = 0.07). Missense mutations of p53 were detected in 20 (51.3%) patients and had a significantly stronger COX-2 expression than tumours without p53 mutation (P = 0.016). Our results suggest a link between p53 mutation and COX-2 overexpression in gastric cancer.
Adult↗
Helicobacter pylori and nonsteroidal anti-inflammatory drugs: a three-way debate.
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Anti-Bacterial Agents↗
Helicobacter pylori and nonsteroidal anti-inflammatory drugs. Approaching the end of the controversy in the new millennium, or room for more debate?
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Anti-Inflammatory Agents, Non-Steroidal↗
Helicobacter pylori and nonsteroidal anti-inflammatory drugs.
The complex interaction between H. pylori and NSAIDs implies that it is over simplistic to conclude that their relationship is independent, synergistic, or antagonistic without considering the influence of other factors. Factors such as previous exposure to NSAIDs, a history of ulcer complication, concurrent use of acid-suppressant therapy, and the difference between NSAIDs and low-dose aspirin all affect the outcome. Several recommendations can be made with regard to the indications of H. pylori eradication for patients requiring NSAIDs. First, patients taking NSAIDs who have ulcers or previous ulcer disease should be tested for the bacterium, and it should be eradicated if present because it is impossible to determine whether the ulcers are caused by H. pylori or NSAIDs or both. Antiulcer drugs should be prescribed to prevent ulcer recurrence for patients who continue to require NSAIDs. Although the efficacy of omeprazole is enhanced by H. pylori infection, it is not justified to leave a pathogen in the stomach in exchange for a modest therapeutic gain. Second, for patients who take low-dose aspirin, eradication of H. pylori substantially reduces the risk of ulcer bleeding. It is advisable that patients taking low-dose aspirin who are at risk of ulcer bleeding should be tested for H. pylori and treated for it if the infection is found. Third, for patients who are about to start NSAIDs, screen-and-treat H. pylori has the potential of reducing the ulcer risk at an affordable incremental cost. It might be argued that any interaction between H. pylori and NSAIDs would become irrelevant in the era of COX-2-selective NSAIDs. Even among patients who are receiving a COX-2-selective NSAID, however, a large-scale study showed that the ulcer risk is significantly higher in H. pylori-positive patients than in uninfected patients. This finding suggests that the relative importance of H. pylori in ulcer development might increase with a reduced toxicity of COX-2-selective NSAIDs. With an increasing use of low-dose aspirin for cardiovascular prophylaxis, the problem of aspirin-related ulcer disease is expected to rise. Given the significant role of H. pylori in the latter condition, screen-and-treat H. pylori might be a useful strategy for the prevention of ulcer complications in high-risk patients receiving low-dose aspirin in the future.
Anti-Inflammatory Agents, Non-Steroidal↗
Up-regulation of cyclooxygenase-1 and -2 in human gastric ulcer.
BACKGROUND: The expression of cyclooxygenase (COX) in human gastric ulcers is unknown. AIM: To study the expression and cellular localization of cyclooxygenase in human gastric ulcers. METHODS: A total of 38 surgical gastric ulcer specimens were studied; 20 were Helicobacter pylori-positive and 18 were associated with NSAID use. Twenty non-ulcerated, histologically normal gastric specimens were used as controls. The cellular localization of COX-1 and COX-2 were determined by immunohistochemistry and double immunofluorescence. Cyclooxygenase messenger RNA (mRNA) was measured by reverse transcription-polymerase chain reaction and localized by in situ hybridization. RESULTS: In control specimens, COX-1 was detected in stromal cells in the lamina propria. There was focal and weak immunostaining for COX-2 in the foveolar epithelium. At the ulcer edge, COX-1 was significantly increased in lamina propria cells whereas COX-2 was strongly expressed in the hyperplastic foveolar epithelium in H. pylori- and non-steroidal anti-inflammatory drugs (NSAID)-associated ulcers. At the ulcer base, there was strong expression of COX-1 and COX-2 in myofibroblasts, macrophages and endothelial cells in the granulation tissue, irrespective of H. pylori status or NSAID use. Messenger RNA of COX-1 and COX-2 were demonstrated by reverse transcription-polymerase chain reaction. Double immunofluorescence and in situ hybridization confirmed the cellular localization of cyclooxygenase at protein and mRNA levels, respectively. CONCLUSION: Both COX-1 and COX-2 are up-regulated in human gastric ulcers.
Adult↗
Randomized trial of low-dose misoprostol and naproxen vs. nabumetone to prevent recurrent upper gastrointestinal haemorrhage in users of non-steroidal anti-inflammatory drugs.
BACKGROUND: Prophylactic misoprostol or non-steroidal anti-inflammatory drugs (NSAIDs) with low gastric toxicity (nabumetone) has been shown to reduce mucosal injury. AIM: To compare nabumetone vs. co-therapy of naproxen with low-dose misoprostol for secondary prevention of upper gastrointestinal bleeding in NSAID users. METHODS: NSAID users presenting with upper gastrointestinal bleeding were enrolled if they required long-term NSAIDs. After ulcer healing, they were randomized to receive: naproxen (500-1000 mg/day) and misoprostol (200 microg b.d.), or nabumetone (1000-1500 mg/day) and placebo misoprostol for 24 weeks. The primary end-point was recurrent upper gastrointestinal bleeding. The secondary end-point was the proportion of patients suffering from major gastrointestinal events including ulcer bleeding, symptomatic ulcers and severe dyspepsia. RESULTS: A total of 90 patients were included in the intention-to-treat analysis (misoprostol/naproxen 45, nabumetone 45). Recurrent bleeding occurred in 10 patients (22.2%) receiving misoprostol/naproxen compared with three (6.7%) receiving nabumetone (relative risk 3.33, 95% CI: 0.98-11.32, P=0.069). The proportion of patients suffering from major gastrointestinal events at 24 weeks was 31.1% in the misoprostol/naproxen group and 28.9% in the nabumetone group. CONCLUSIONS: Misoprostol/naproxen is not superior to nabumetone for secondary prevention of upper gastrointestinal bleeding. Neither low-dose misoprostol nor nabumetone is adequate for high-risk NSAID users.
Adult↗
Validation of a new immunoblot assay for the diagnosis of Helicobacter pylori in the Asian population.
BACKGROUND: Performance of commercial serological tests for Helicobacter pylori varies in different populations, largely due to strain heterogeneity and variations in antigenic preparations. Currently available serology tests often show sub-optimal accuracy when used for Asian patients. AIM: This study evaluated a recombinant antigen-based immunoblot for the diagnosis of H. pylori infection in Chinese patients, and compared it with a conventional ELISA test. METHODS: Dyspeptic patients referred for diagnostic endoscopy were recruited. The gold standard for H. pylori infection was based on two or more positive results among rapid urease test, histology and (13)C-urea breath test. Serological diagnosis of H. pylori infection was conducted by an ELISA test (pylori DTect; Diagnostic Technology) and an immunoblotting against a novel recombinant antigen (C1S; Genelab), which was constructed by immunological screening of the genomic DNA library of H. pylori. RESULTS: A total of 87 patients were evaluated and H. pylori infection was diagnosed in 40 (46%) by the reference tests. The sensitivities of the ELISA and immunoblot were 80% (95% CI: 64--91%) and 90% (95% CI: 76--97%), whilst the specificities were 96% (95% CI: 86--96%) and 87% (95% CI: 74--95%), respectively. The respective likelihood ratios of the two tests were 18.6 and 7.0. CONCLUSIONS: Satisfactory performance is obtained by the use of the new recombinant antigen-based immunoblot for diagnosing H. pylori infection in Chinese patients.
Adult↗
Expression and cellular localization of COX-1 and -2 in Helicobacter pylori gastritis.
BACKGROUND: There are conflicting reports on the expression of cyclooxygenase in Helicobacter pylori infection. AIM: To evaluate the expression of COX-1 and COX-2 in H. pylori gastritis at messenger RNA (mRNA) and protein levels. METHODS: Endoscopic gastric biopsies were obtained from patients with non-ulcer dyspepsia. The levels of COX-1 and COX-2 mRNA were compared between H. pylori-infected and uninfected specimens using reverse transcription-polymerase chain reaction. The immunohistochemical findings were correlated with the cellular localization of cyclooxygenase mRNA using in situ hybridization. RESULTS: A total of 40 H. pylori-infected and 40 uninfected specimens were studied. mRNA of COX-2 but not COX-1 was elevated in H. pylori-infected mucosa. COX-1 was localized to the mononuclear inflammatory, endothelial and smooth muscle cells in the lamina propria. COX-2 was barely detectable in uninfected mucosa but was strongly expressed in the foveolar and glandular epithelia in H. pylori gastritis. CONCLUSION: Cyclooxygenase-1 is expressed in the mononuclear inflammatory, endothelial and smooth muscle cells in the lamina propria irrespective of the H. pylori status. By contrast, H. pylori induces COX-2 expression in the foveolar and glandular epithelia.
Adult↗
Effect of Helicobacter pylori eradication on expression of cyclin D2 and p27 in gastric intestinal metaplasia.
BACKGROUND AND AIMS: Cyclins and cyclin-dependent kinase inhibitors play a crucial role in the control of cell cycle transitions. Enhanced expression of cyclin D2 and reduced expression of p27kip1 (p27) have been implicated in the pathogenesis of cancer. Because intestinal metaplasia has been regarded as a pre-malignant lesion, we investigated the expression of cyclin D2 and p27 in Helicobacter pylori-associated chronic gastritis with and without intestinal metaplasia, and followed the changes after H. pylori eradication. METHODS: Expression of cyclin D2 and p27 was studied by immunohistochemistry in 59 patients (including 35 patients with intestinal metaplasia) and in 10 gastric cancer patients. Among them, 29 H. pylori-infected patients had serial gastric biopsies taken before and at 1-year after eradication of H. pylori. RESULTS: Expression of cyclin D2 was significantly higher in gastric cancers when compared to their adjacent non-tumour tissues (median score 3 vs. 1, P=0.015). Over-expression of cyclin D2 was detected in H. pylori-associated chronic gastritis and intestinal metaplasia, which was reduced after eradication of the organism (median score 2 vs. 1, P=0.037 in chronic gastritis; median score 2 vs. 0, P=0.008 in intestinal metaplasia). While the normal gastric mucosa showed strong p27 expression, five of the 10 gastric cancer tissues exhibited reduced p27 expression (P=0.039). Diminished p27 expression was also seen in intestinal metaplasia, which was restored 1-year after H. pylori eradication (eight out of 16 vs. one out of 16, P=0.018). Reduced expression of p27 was frequently associated with increased cyclin D2 expression in H. pylori-associated intestinal metaplasia (P=0.02). CONCLUSION: Over-expression of cyclin D2 and reduced expression of p27 are closely linked to H. pylori-associated intestinal metaplasia. Eradication of H. pylori infection reverses the aberrant expression of cyclin D2 and p27 in intestinal metaplasia.
Cyclin D2↗
Apoptosis and proliferation in Helicobacter pylori-associated gastric intestinal metaplasia.
BACKGROUND: Imbalance between apoptosis and proliferation may be one of the mechanisms underlying H. pylori associated gastric carcinogenesis. AIM: To examine the cell kinetics of gastric intestinal metaplasia and the effect of H. pylori eradication. METHODS: Endoscopic gastric biopsies were obtained from 100 H. pylori-infected patients. Apoptosis was determined by triphosphate nick-end labelling (TUNEL) and apoptotic nuclei counting, whereas proliferation was assessed by Ki67 immunostaining. Gastric biopsies were repeated in a sub-group of intestinal metaplasia patients after H. pylori eradication. RESULTS: Antral apoptotic index was significantly lower in intestinal metaplasia than in non-intestinal metaplasia (0.19% vs. 0.51%; P < 0.0001) whereas the level of proliferation was comparable (28% vs. 22%, P=0.15). Serial antral biopsies taken from 14 intestinal metaplasia patients before and 1 year after H. pylori eradication showed a significant drop in proliferation in both intestinal metaplasia (50% vs. 12%, P < 0.001) and non-intestinal metaplasia area (47% vs. 9%, P < 0.001). A similar fall in apoptosis was detected in non-metaplastic region (0.58% vs. 0.38%, P < 0.001) but not in intestinal metaplasia (0.24% vs. 0.27%, P=0.56), resulting in a significant increase in the apoptosis/proliferation ratio (0.005-0.021; P=0.03). CONCLUSIONS: Dysregulation in apoptosis control of gastric intestinal metaplasia may contribute to gastric carcinogenesis, which may be retarded by clearance of H. pylori.
Adult↗
Lamivudine treatment for fulminant hepatic failure due to acute exacerbation of chronic hepatitis B infection.
BACKGROUND: Exacerbation of chronic hepatitis B infection can lead to fulminant hepatic failure with a mortality of up to 90%. AIM: To evaluate the efficacy of lamivudine in the treatment of this subgroup of patients. METHODS: Twenty-four patients with exacerbation of chronic hepatitis B infection and fulminant hepatic failure were treated with lamivudine, 100 mg daily. Hepatitis A, C, D and human immunodeficiency virus co-infections and hepatocellular carcinoma were excluded. RESULTS: The median age was 53 years (range, 24-77 years) with a male predominance of 20:4. Seventeen patients were hepatitis B e antigen positive. Mean hepatitis B virus DNA was 2079 Meq/mL. Eight patients (33%) survived (group A). Thirteen patients died and three patients received liver transplantation (67%) (group B). Baseline laboratory results were comparable between the two groups, including serum albumin, bilirubin, alanine aminotransferase, prothrombin time and creatinine. Group B patients had significantly more comorbid illnesses at baseline and more complications, including sepsis and renal failure, compared with group A patients. Six out of eight survivors (75%) had full hepatitis B e antigen seroconversion, but this was not sustained in four patients. CONCLUSIONS: Lamivudine may be useful in treating patients with fulminant hepatic failure due to exacerbation of chronic hepatitis B. Hepatitis B e antigen seroconversion was less durable in this subgroup of patients and long-term therapy may be required.
Administration, Oral↗